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      Improved final predicted height with the injection of leuprolide in children with earlier puberty: A retrospective cohort study

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          Abstract

          The adult height of children with early onset puberty is limited by the premature maturation of hypothalamic-pituitary-gonadal axis. To evaluate the effects of gonadotropin-releasing hormone analog (GnRHa) treatment on the final height (FH) and bone maturation rate (BMR) in girls with early puberty (EP) or idiopathic central precocious puberty (ICPP), we examined data from girls who were diagnosed with EP or ICPP and underwent GnRHa (Leuplin Depot: 3.75 mg/month) at China Medical University Hospital, in Taiwan, between 2006 and 2015. Patients were observed until the achievement of FH and divided into an “EP group” (T-ep) and “ICPP group” (T-icpp) according to the age of onset of puberty. Eighty-seven patients were enrolled (T-ep, N = 44, puberty onset at 8–10 years; T-icpp, N = 43, puberty onset before 8 years). The demographic data of girls with EP or IPP was characterized. BMR, change in predicted final height (PFH) after GnRHa treatment, target height (TH) and FH were measured. After GnRHa treatment, the study groups (T-ep: 160.24±6.18 cm, T-icpp: 158.99±5.92 cm) both had higher PFH than at initiation (T-ep: 159.83±7.19 cm, T-icpp: 158.58±5.93 cm). There was deceleration of BMR in both groups (T-ep: 0.57±0.39; T-icpp: 0.97±0.97) and a significant difference between the groups (p = 0.027). The gap in FH standard deviation scores (SDS) and TH SDS had a significant difference in T-ep (p = 0.045) but not in T-icpp. Moreover, there was no difference in the gap of PFH SDS between the 1 st and final treatment in both groups. We concluded that GnRHa decelerated BMR in girls with earlier puberty. Further prospective clinical studies are warranted.

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          Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards.

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            Early age at menarche associated with cardiovascular disease and mortality.

            The relationship between age at menarche and cardiovascular disease remains unclear. Two recent studies found an inverse association between age at menarche and all-cause mortality. The aim of this study was to examine the relationship between age at menarche and cardiovascular disease risk factors, events, and mortality. A population-based prospective study involving 15,807 women, aged 40-79 yr in 1993-1997 and followed up to March 2007 for cardiovascular disease events (median follow-up 10.6 yr) and February 2008 for mortality (median follow-up 12.0 yr) was used. Odds ratios for cardiovascular disease risk factors and hazard ratios for incident cardiovascular disease and mortality were calculated. There were 3888 incident cardiovascular disease events (1323 coronary heart disease, 602 stroke, and 1963 other) and 1903 deaths (640 cardiovascular disease, 782 cancer, and 481 other) during follow-up. Compared with other women, those who had early menarche (<12 yr) had higher risks of hypertension [1.13 (1.02-1.24)], incident cardiovascular disease [1.17 (1.07-1.27)], incident coronary heart disease [1.23 (1.06-1.43)], all-cause mortality [1.22 (1.07-1.39)], cardiovascular disease mortality [1.28 (1.02-1.62)], and cancer mortality [1.25 (1.03-1.51)], adjusted for age, physical activity, smoking, alcohol, educational level, occupational social class, oral contraceptive use, hormone replacement therapy, parity, body mass index, and waist circumference. Early age at menarche (before age 12 yr) was associated with increased risk of cardiovascular disease events, cardiovascular disease mortality, and overall mortality in women, and this association appeared to be only partly mediated by increased adiposity.
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              Recent Secular Trends in Pubertal Timing: Implications for Evaluation and Diagnosis of Precocious Puberty

              The decline in age at puberty in the general population has been paralleled by an increase in the number of girls referred for evaluation of precocious puberty (PP). In 1999, The Lawson Wilkins Pediatric Endocrine Society recommended a lowering of the age limit for evaluation of PP in girls. However, the limited evidence on which these recommendations were based led many experts to question these new suggestions. The emergence of new European pubertal timing data evaluated by robust clinical as well as biochemical markers has broadened our insight on how to interpret the recent pubertal changes. The recent pubertal trends have resulted in a concomitant lowering of the lower limit of normality of the pubertal onset. However, evidence suggests that age at the gonadotropin and sex steroid surges have not changed. Thus, it looks as if an increasing proportion of contemporary early pubertal girls may experience isolated gonadotropin-independent thelarche rather than central PP, which may not be discernible on pubertal examination alone. Thus, the population-based limits of normality should not be directly translated into revision of age limits for evaluation of PP due to the risk of misdiagnosing rapid progressive PP as well as intracranial and other underlying pathology.
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                Author and article information

                Contributors
                Role: Data curationRole: InvestigationRole: Writing – original draft
                Role: Formal analysisRole: Software
                Role: MethodologyRole: Resources
                Role: Writing – review & editing
                Role: Resources
                Role: Formal analysisRole: Software
                Role: ConceptualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 October 2017
                2017
                : 12
                : 10
                : e0185080
                Affiliations
                [1 ] Department of Chinese Medicine, China Medical University Hospital, Taichung City, Taiwan
                [2 ] Department of Public Health, Doctoral Program, China Medical University, Taichung, Taiwan
                [3 ] Department of Genetics and Metabolism, Children’s Hospital of China Medical University, Taichung, Taiwan
                [4 ] Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
                [5 ] School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
                [6 ] Department of Biotechnology, Asia University, Taichung, Taiwan
                [7 ] Department of Public Health, China Medical University, Taichung, Taiwan
                Universite de Rouen, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-6770-4246
                Article
                PONE-D-17-04380
                10.1371/journal.pone.0185080
                5626117
                28973010
                853e782a-1a82-4b50-a476-7e1311b0b69a
                © 2017 Lin et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 February 2017
                : 6 September 2017
                Page count
                Figures: 3, Tables: 3, Pages: 11
                Funding
                The study was supported by grants from the China Medical University Hospital (DMR-103-040).
                Categories
                Research Article
                Medicine and Health Sciences
                Endocrinology
                Endocrine Physiology
                Puberty
                Biology and Life Sciences
                Physiology
                Endocrine Physiology
                Puberty
                Medicine and Health Sciences
                Physiology
                Endocrine Physiology
                Puberty
                People and Places
                Population Groupings
                Age Groups
                Children
                People and Places
                Population Groupings
                Families
                Children
                Medicine and Health Sciences
                Endocrinology
                Pediatric Endocrinology
                Medicine and Health Sciences
                Pediatrics
                Pediatric Endocrinology
                Medicine and Health Sciences
                Endocrinology
                Endocrine Physiology
                Menstrual Cycle
                Menarche
                Biology and Life Sciences
                Physiology
                Endocrine Physiology
                Menstrual Cycle
                Menarche
                Medicine and Health Sciences
                Physiology
                Endocrine Physiology
                Menstrual Cycle
                Menarche
                Biology and Life Sciences
                Physiology
                Reproductive Physiology
                Menstrual Cycle
                Menarche
                Medicine and Health Sciences
                Physiology
                Reproductive Physiology
                Menstrual Cycle
                Menarche
                Medicine and Health Sciences
                Pediatrics
                People and Places
                Geographical Locations
                Asia
                Taiwan
                Medicine and Health Sciences
                Diagnostic Medicine
                Medicine and Health Sciences
                Endocrinology
                Custom metadata
                All relevant data are within the paper.

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